G1 and G2 cell-cycle arrest following microtubule depolymerization in human breast cancer cells

April L. Blajeski, Vy A. Phan, Timothy J. Kottke, Scott H Kaufmann

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

Microtubule-depolymerizing agents are widely used to synchronize cells, screen for mitotic checkpoint defects, and treat cancer. The present study evaluated the effects of these agents on normal and malignant human breast cell lines. After treatment with 1 μM nocodazole, seven of ten breast cancer lines (type A cells) arrested in mitosis, whereas the other three (type B cells) did not. Similar effects were observed with 100 nM vincristine or colchicine. Among five normal mammary epithelial isolates, four exhibited type A behavior and one exhibited type B behavior. Further experiments revealed that the type B cells exhibited a biphasic dose-response curve, with mitotic arrest at low drug concentrations (100 nM nocodazole or 6 nM vincristine) that failed to depolymerize microtubules and a p53-independent p21waf1/cip1-associated G1 and G2 arrest at higher concentrations (1 μM nocodazole or 100 nM vincristine) that depolymerized microtubules. Collectively, these observations provide evidence for coupling of premitotic cell-cycle progression to microtubule integrity in some breast cancer cell lines (representing a possible "microtubule integrity checkpoint") and suggest a potential explanation for the recently reported failure of some cancer cell lines to undergo nocodazole induced mitotic arrest despite intact mitotic checkpoint proteins.

Original languageEnglish (US)
Pages (from-to)91-99
Number of pages9
JournalJournal of Clinical Investigation
Volume110
Issue number1
DOIs
StatePublished - 2002

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G2 Phase Cell Cycle Checkpoints
G1 Phase Cell Cycle Checkpoints
Nocodazole
Microtubules
Breast Neoplasms
Vincristine
M Phase Cell Cycle Checkpoints
Cell Line
Breast
B-Lymphocytes
Colchicine
Mitosis
Neoplasms
Cell Cycle
Pharmaceutical Preparations
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

G1 and G2 cell-cycle arrest following microtubule depolymerization in human breast cancer cells. / Blajeski, April L.; Phan, Vy A.; Kottke, Timothy J.; Kaufmann, Scott H.

In: Journal of Clinical Investigation, Vol. 110, No. 1, 2002, p. 91-99.

Research output: Contribution to journalArticle

Blajeski, April L. ; Phan, Vy A. ; Kottke, Timothy J. ; Kaufmann, Scott H. / G1 and G2 cell-cycle arrest following microtubule depolymerization in human breast cancer cells. In: Journal of Clinical Investigation. 2002 ; Vol. 110, No. 1. pp. 91-99.
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